[Thieno[2,3-c]quinolines - synthesis and biological investigation]

Pharmazie. 2004 Jun;59(6):439-42.
[Article in German]

Abstract

pH-Dependant reduction of the methyl 3-(2-nitrophenyl)thiophene-2-carboxylate (3), obtained by Suzuki cross-coupling of the methyl 3-iodothiophene-2-carboxylate with 2-nitrophenyl boronic acid yields the cyclic hydroxamic acid 4 and the lactam 5, respectively. The lactam 5 is also formed by reacting the compound 2 with pinacolato 2-aminophenylboronate. The 4-chlorothieno[2,3-c]quinoline 6 is formed from the lactam 5 by heating with POCl3/PCl5. Melting of 6 with the novaldiamine base in phenol gives the chloroquine analogue 7, whereas the amodiaquine and the cycloquine analogues 8 and 9 are obtained using phenol Mannich bases. The hydroxamic acid 4 has a moderate effect on eicosanoid biosynthesis in human whole blood. The growth of the chloroquine resistent Plasmodium falciparum strain Dd2 is inhibited by the pyronaridine derivative 9 with an IC50 value of 650 nM.

Publication types

  • English Abstract

MeSH terms

  • Animals
  • Antimalarials / chemical synthesis*
  • Antimalarials / pharmacology*
  • Eicosanoids / biosynthesis
  • Hydrogen-Ion Concentration
  • Hydroxamic Acids / pharmacology
  • Indicators and Reagents
  • Lactams / chemical synthesis
  • Lactams / pharmacology
  • Mannich Bases
  • Plasmodium falciparum / drug effects
  • Quinolines / chemical synthesis*
  • Quinolines / pharmacology*

Substances

  • Antimalarials
  • Eicosanoids
  • Hydroxamic Acids
  • Indicators and Reagents
  • Lactams
  • Mannich Bases
  • Quinolines